Herb-Drug Interaction of 50 Chinese Herbal Medicines on CYP3A4 Activity in Vitro and in Vivo

The purpose of this study is to evaluate the effects of Chinese herbal medicines on the enzymatic activity of CYP3A4 and the possible metabolism-based herb-drug interactions in human liver microsomes and in rats. Fifty single-herbal preparations were screened for the activity of CYP3A4 using human liver microsomes for an in vitro probe reaction study. The enzymatic activity of CYP3A4 was estimated by determing the 6β-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Huang Qin (Scutellaria baicalensis Geprgi), Mu Dan Pi (Paeonia suffruticosa Andr.), Ji Shiee Terng (Spatholobus suberectus Dunn.) and Huang Qi (Astragalus membranaceus [Fisch] Bge) have been demonstrated to have remarkable inhibiting effects on the metabolism of CYP3A4, whereas Xi Yi Hua (Magnolia biondii Pamp.) exhibited a moderate inhibition. These five single herbs were further investigated in an animal study using midazolam. Mu Dan Pi, Ji Shiee Terng and Huang Qi were observed to have greatly increased in the C max and AUC of midazolam. This study provides evidence of possible herb-drug interactions involved with certain single herbs.

Download Full-text

Application of Human Liver Microsomes in Metabolism-Based Drug-Drug Interactions: In Vitro-in Vivo Correlations and the Abbott Laboratories Experience

Advances in Pharmacology ◽

10.1016/s1054-3589(08)60202-1 ◽

1997 ◽

pp. 65-101 ◽

Cited By ~ 23

Author(s):

A. David Rodrigues ◽

Shekman L. Wong

Keyword(s):

Drug Interactions ◽

Human Liver ◽

Liver Microsomes ◽

Human Liver Microsomes

Download Full-text

Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/650718 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Hye Young Ji ◽

Kwang Hyeon Liu ◽

Ji Hyeon Jeong ◽

Dae-Young Lee ◽

Hyun Joo Shim ◽

...

Keyword(s):

Cytochrome P450 ◽

Human Liver ◽

Liver Microsomes ◽

Human Liver Microsomes ◽

Udp Glucuronosyltransferase ◽

Index Value ◽

Tuber Extract ◽

Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

Download Full-text

IN VITRO METABOLISM OF THE CALMODULIN ANTAGONIST DY-9760e (3-[2-[4-(3-CHLORO-2-METHYLPHENYL)-1-PIPERAZINYL]ETHYL]-5,6-DIMETHOXY-1-(4-IMIDAZOLYLMETHYL)-1H-INDAZOLE DIHYDROCHLORIDE 3.5 HYDRATE) BY HUMAN LIVER MICROSOMES: INVOLVEMENT OF CYTOCHROMES P450 IN ATYPICAL KINETICS AND POTENTIAL DRUG INTERACTIONS

Drug Metabolism and Disposition ◽

10.1124/dmd.105.004903 ◽

2005 ◽

Vol 33 (11) ◽

pp. 1628-1636 ◽

Cited By ~ 5

Author(s):

Shuko Tachibana ◽

Yuko Fujimaki ◽

Hiroyuki Yokoyama ◽

Osamu Okazaki ◽

Ken-ichi Sudo

Keyword(s):

Drug Interactions ◽

Human Liver ◽

Cytochromes P450 ◽

Liver Microsomes ◽

Human Liver Microsomes ◽

In Vitro Metabolism ◽

Potential Drug ◽

Calmodulin Antagonist

Download Full-text

Rapid identification of MDMB-CHMINACA metabolites using Zebrafish and Human Liver microsomes as the Biotransformation system by LC-QE-HF-MS

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa001 ◽

2020 ◽

Cited By ~ 2

Author(s):

Duo-qi Xu ◽

Yong Dai ◽

Wen-fang Zhang ◽

Ji-fen Wang ◽

Yan-yan Wang ◽

...

Keyword(s):

Animal Model ◽

Human Liver ◽

Mass Measurement ◽

Liver Microsomes ◽

Rapid Identification ◽

Human Liver Microsomes ◽

Designer Drugs ◽

Published Data

Abstract MDMB-CHMINACA is a newly synthetic cannabinoid which scoped in NMS Lab, USA. Since there are currently no published data on MDMB-CHMINACA metabolism, we aimed to identify its biotransformation pathways and major metabolites. Liquid chromatography Q-Extractive HF Hybrid Quadrupole-Orbitrap mass spectrometry (LC-QE-HF-MS) using full scan positive ion mode and targeted MS/MS (ddms2) techniques with accurate mass measurement were employed to analyze the metabolic sites and pathways. An in vivo metabolic animal model of zebrafish was established to verify the metabolic pathways of MDMB-CHMINACA obtained from human liver microsomal experiment in vitro. The results showed that 29 metabolites were generated in the zebrafish animal model and human liver microsomes model. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, minor reactions also occurred at the tert-butyl chain, and no reaction was analysised at the indazole ring. We recommend M1 group (MDMB-CHMINACA ester hydroxylation), and M2 group (MDMB-CHMINACA monohydroxylation) as the potential poisoning markers to document MDMB-CHMINACA intake in clinical and forensic cases. Additionally, this study provides preliminary information regarding the metabolism of MDMB-CHMINACA that will guide analytical standard manufacturers to better provide suitable references for further studies on newly encountered designer drugs.

Download Full-text

In-Vitro CYP3A4, CYP2E1 and UGT Activity in Human Liver Microsomes by Strobilanthes crispus Leaf Extracts

The Natural Products Journal ◽

10.2174/2210315509666190304124328 ◽

2020 ◽

Vol 10 (2) ◽

pp. 104-112

Author(s):

Gabriel Akyirem Akowuah ◽

Jin Han Chin ◽

Siew Wei Yeong ◽

Suk Yen Quah ◽

Mariam Ahmad

Keyword(s):

Drug Interactions ◽

Human Liver ◽

Liver Microsomes ◽

Significant Inhibition ◽

Human Liver Microsomes ◽

Cyp3a4 Activity ◽

Leaf Extracts ◽

Strobilanthes Crispus ◽

Glucuronosyl Transferase

Background: Strobilanthes crispus (L.) Bremek (Acanthaceae) leaves are used traditionally in Malaysia, Thailand, and Indonesia for anti-diabetic, anti-lytic, diuretic, and laxative purposes. Herb-drug interactions may potentiate or antagonize the absorption and metabolism of drugs which may result in potential toxicity. The aim of the present study was to investigate the effect of juice, hot aqueous, cold aqueous and methanol extracts of S. crispus leaves on phase I cytochrome 3A4 (CYP3A4) and Cytochrome 2E1 (CYP2E1) and phase II human liver enzyme UDP-Glucuronosyl Transferase (UGT). Methods: The herb-drug interactions of the leaf extracts and juice were determined by specific enzyme activity of CYP isoforms with specific probe substrate using spectrophotometry. CYP3A4 activity was measured for aminopyrine specific metabolite (formaldehyde) at 415 nm. CYP2E1 activity was determined using p-nitrophenol specific metabolite (p-nitrocatechol) at 535 nm. UGT activity was quantified through the consumption of p-nitrophenol by UGT at 405 nm. Results: All the S. crispus preparations showed significant inhibition of CYP3A4 activity. Only the methanolic extract showed a significant inhibition in CYP2E1. All the S. crispus extracts showed a significant effect on UGT activation at the higher concentration (1000 ng/ml). Only the cold aqueous extract and the juice showed UGT inhibition at lower concentration (1 ng/ml). Conclusion: S. crispus preparations showed in-vitro drug-herb interaction effects on human liver microsomes. Therefore, there is a possibility of drug-herb interaction could occur with S. crispus leaves through its effect on CYP3A4. Inhibition of the herb extracts on CYP2E1 could show anticarcinogenesis effects. The potency of drugs that metabolized via UGT pathway may be affected when co-administered with S. crispus leaf preparations.

Download Full-text